Alteration of Cholinergic System in Keratinocytes Cells Produces Acantholysis: A Possible Use of Cholinergic Drugs in Pemphigus Vulgaris

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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Alteration of Cholinergic System in Keratinocytes Cells Produces Acantholysis: A Possible Use of Cholinergic Drugs in Pemphigus Vulgaris



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 11(3): 238-242.

Author(s): Luca Fania, Anna Zampetti, Giuseppe Guerriero and Claudio Feliciani.

Affiliation: Department of Dermatology, Policlinico A. Gemelli, Largo Gemelli 8, 00168 Rome, Italy.

Abstract

Human epidermis shows a non-neuronal cholinergic system including keratinocyte (kc) acetylcholine (Ach) axis which is composed by enzymes and two families of Ach receptors (muscarinic and nicotinic receptors). The activity of these two receptors can regulate the interkeratinocytes and kcs-extracellular matrix adhesion modifying the regulation of intercellular adhesion molecules like cadherins and integrins. Some authors demonstrate that acantholysis in pemphigus depends not only on anti desmogleins antibodies (abs) (mostly IgG) but even on other abs directed against kc membrane antigens (e.g. anti Ach receptors Abs). In the early phase of pemphigus pathogenesis, anti Ach receptors Abs block Ach signaling essential for cell shape and intercellular adhesion and increase the phosphorylation of adhesion molecules. Combined with the action of abs antidesmogleins, anti Ach receptors Abs cause the acantholytic phenomenon. In vitro experiments show that high doses of Ach in acantholytic kcs can rapidly reverse this pathologic event. In vivo experiments using neonatal mice model of Pemphigus have demonstrated that cholinergic agonists reduce these lesions. Therapy with pyridostigmine bromide and Nicotinamide per os or pilocarpine used topically, drugs that present cholinomimetic effects, has lead to encouraging results in patients affected by Pemphigus disease. Cholinergic agents could have a strategic role in the therapy of pemphigus since they could be responsible for the early stage of acantholytic diseases.

Keywords:

Acantholysis, cholinergic drugs, cholinergic system in keratinocytes cells.



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Article Details

Volume: 11
Issue Number: 3
First Page: 238
Last Page: 242
Page Count: 5
DOI: 10.2174/1871523011202030238
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